8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of Earliest Event Reported): November 7, 2019

 

 

Allena Pharmaceuticals, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

DELAWARE   001-38268   45-2729920

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

 

One Newton Executive Park, Suite 202

Newton, Massachusetts

  02462
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code (617) 467-4577

Not Applicable

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered or to be registered pursuant to Section 12(b) of the Act.

 

Title of each class

 

Trading

symbol(s)

 

Name of each exchange

on which registered

Common Stock, par value $0.001 per share   ALNA   The Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☒

 

 

 


Item 7.01

Regulation FD Disclosure.

On November 7, 2019, Allena Pharmaceuticals, Inc. (the “Company”) conducted a conference call reviewing topline results from URIROX-1, the Company’s first Phase 3 pivotal trial evaluating reloxaliase, an orally-administered, recombinant oxalate-degrading enzyme therapeutic candidate, in patients with enteric hyperoxaluria (“EH”), as well as additional data from Study 206, the Company’s Phase 2 trial evaluating reloxaliase in high-risk patients with EH and advanced chronic kidney disease (“CKD”). A copy of the presentation slide deck is being furnished as Exhibit 99.2 to this Report on Form 8-K.

The information in this report furnished pursuant to Item 7.01 shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. It may only be incorporated by reference in another filing under the Exchange Act or the Securities Act of 1933, as amended, if such subsequent filing specifically references the information furnished pursuant to Item 7.01 of this report

 

Item 8.01

Other Events.

On November 7, 2019, the Company issued a press release announcing topline results from URIROX-1, the Company’s first Phase 3 pivotal trial evaluating reloxaliase, an orally-administered, recombinant oxalate-degrading enzyme therapeutic candidate, in patients with EH, as well as additional data from Study 206, the Company’s Phase 2 trial evaluating reloxaliase in high-risk patients with EH and advanced CKD. A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

 

Item 9.01.

Financial Statements and Exhibits.

(d) Exhibits

 

Exhibit
No.

  

Description

99.1    Press Release by Allena Pharmaceuticals, Inc. dated November 7, 2019
99.2    Investor Presentation dated November 7, 2019 furnished by Allena Pharmaceuticals, Inc.


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: November 7, 2019     Allena Pharmaceuticals, Inc.
    By:  

/s/ Edward Wholihan

      Edward Wholihan
      Chief Financial Officer
EX-99.1

Exhibit 99.1

 

LOGO

Allena Pharmaceuticals Reports Positive Reloxaliase Topline Results from URIROX-1 Trial and from Study 206

Phase 3 URIROX-1 Trial Achieves Primary Endpoint with Statistically Significant Reduction in Urinary Oxalate in Patients with Enteric Hyperoxaluria

Phase 2 Study 206 Trial Demonstrates Substantial Plasma Oxalate Reduction in Patients with Enteric Hyperoxaluria and Advanced Chronic Kidney Disease

Allena to Present Results at the American Society of Nephrology Kidney Week 2019

Allena to Host Conference Call Today at 8:30 a.m. EST

NEWTON, Mass., November 7, 2019 — Allena Pharmaceuticals, Inc. (NASDAQ: ALNA), a late-stage, biopharmaceutical company dedicated to developing and commercializing first-in-class, oral enzyme therapeutics to treat patients with rare and severe metabolic and kidney disorders, today announced positive topline results from URIROX-1, its first Phase 3 pivotal trial evaluating reloxaliase in patients with enteric hyperoxaluria (EH), as well as additional data from Study 206, its Phase 2 trial evaluating reloxaliase in high-risk patients with EH and advanced chronic kidney disease (CKD). In both studies, treatment with reloxaliase led to substantial reductions in measures of oxalate burden. URIROX-1 met its primary endpoint, demonstrating a statistically significant change from baseline in 24-hour urinary oxalate (UOx) excretion compared to placebo (p=0.004).

“We are excited to present positive results from two separate trials of reloxaliase at ASN. The demonstration of reloxaliase’s ability to consistently and significantly reduce UOx for patients in URIROX-1, and also reduce plasma oxalate (POx) in patients with EH and advanced CKD in Study 206, is an important step in the development of reloxaliase as a potential first-in-class therapy for people living with EH,” said Louis Brenner, MD, President and Chief Executive Officer of Allena Pharmaceuticals. “Sharing positive Phase 3 data from our study for a patient population with a high disease burden and without a currently available treatment option represents a key milestone for Allena and the patients we serve. We are grateful for the continued support of our patients, investigators, and partners.”

Dr. Brenner continued, “We look forward to analyzing the full datasets from URIROX-1 and Study 206. We plan to apply these insights to our ongoing clinical development of reloxaliase, including potentially the adaptive design elements of URIROX-2, as we pursue an accelerated approval regulatory strategy. In addition, based on the robust reduction of POx demonstrated in Study 206, we also plan to explore a registrational path for reloxaliase as a potential treatment for patients with EH and advanced CKD, a life threatening condition.”

URIROX-1 Results:

URIROX-1 is a multicenter, global, randomized, double-blind, placebo-controlled study conducted to evaluate the safety and efficacy of reloxaliase in 115 patients for a four-week treatment period. Patients were randomized 1:1 to receive either reloxaliase or placebo and took ~240 mg (equivalent to 7,500 units) of reloxaliase or placebo with each meal or snack three to five times per day.

The study achieved its primary endpoint, with a mean reduction of 22.6% in average 24-hour UOx excretion measured during Weeks 1-4 among patients treated with reloxaliase, compared to 9.7% in the placebo group (least square (LS) mean treatment difference of -14.3%, p=0.004). Additionally, in a pre-specified secondary endpoint, the stratified analysis of the primary endpoint in bariatric surgery patients (68% of the total study population), patients treated with reloxaliase achieved a mean reduction of 21.2% in average 24-hour UOx excretion, compared to 6.0% for patients treated with placebo (LS mean difference of -16.2%, p=0.01).


The lead secondary endpoint evaluated the proportion of patients on reloxaliase with a ³20% reduction from baseline in 24-hour UOx excretion during Weeks 1-4. Across the full study population, the proportion of patients treated with reloxaliase who achieved a ³20% reduction from baseline in 24-hour UOx excretion was 48.3%, compared to 31.6% for patients on placebo (p=0.06). In another pre-specified secondary endpoint, the stratified analysis of the key secondary endpoint in bariatric surgery patients, the proportion of patients on reloxaliase with a ³20% reduction from baseline in 24-hour UOx excretion during Weeks 1-4 was 50.0%, compared to 28.9% for patients on placebo (p=0.036).

Consistent with prior clinical experience, reloxaliase was well tolerated in the URIROX-1 trial. 114 of 115 patients completed the study, and there were no adverse events leading to treatment discontinuation in the reloxaliase group.

“Patients living with EH can experience painful kidney stone episodes and develop deposits of calcium oxalate crystals over time, both of which damage the kidney and can ultimately progress to CKD. The URIROX-1 results demonstrate that reloxaliase degrades oxalate via its gastrointestinal mechanism and has the potential to provide a significant reduction of the oxalate burden on the kidney, a key outcome for patients with EH,” said David S. Goldfarb, M.D., Professor of Medicine and Physiology and Clinical Chief of Nephrology at NYU Langone Health. “With reloxaliase’s favorable tolerability profile and clinically meaningful effect on UOx levels, this novel therapy, if approved, could potentially transform the treatment landscape for EH patients.”

Study 206 Results:

Study 206 is a multi-center, open-label, single-arm Phase 2 clinical trial designed to enroll between 15 and 20 patients in the United States and Europe aged 12 and older. Patients orally administer ~240 mg (equivalent to 7,500 units) of reloxaliase with each meal or snack five times a day, for 12 consecutive weeks.

Study 206 has enrolled patients with EH and advanced CKD, which can lead to systemic oxalosis, a potentially life-threatening condition. This includes end stage renal disease patients who are on dialysis and patients who have undergone kidney transplantation.

 

   

Two patients with CKD Stage 3 demonstrated a substantial reduction in 24-hour UOx excretion over Weeks 4 to 12 (reductions of 29% and 42%). These patients also showed a substantial reduction in POx (reductions of 42% and 16%, respectively).

 

   

Six patients with CKD Stage 5, including five patients on dialysis, demonstrated substantial reductions in POx levels over Weeks 4 to 12 (reductions ranged from 19% to 68%).

 

   

Consistent with prior clinical experience, reloxaliase was generally well tolerated in this population with treatment out to 12 weeks.

“I am incredibly encouraged by these data from Study 206, which build on the interim data reported earlier this year and suggest that reloxaliase improves the outlook for patients with EH and advanced CKD, who are often stuck in a vicious and fatal cycle of kidney damage, dialysis and transplantation,” said Craig Langman, M.D., Head of the Division of Kidney Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago and Isaac A. Abt, M.D. Professor of Kidney Diseases and Pediatrics at Northwestern University Feinberg School of Medicine. “To my knowledge, this is the first demonstration of a successful pharmacologic strategy for POx reduction in patients with EH. I look forward to partnering with Allena as we explore opportunities to potentially expand reloxaliase’s reach to address the full spectrum of EH, including people living with the most severe forms of the disease.”

Data from URIROX-1 and Study 206 will be presented in poster presentations at the ASN Annual Meeting this week in Washington, D.C.

Details are as follows:

 

   

A phase 3, randomized, placebo-controlled trial of reloxaliase in enteric hyperoxaluria (URIROX-1): Clinical characteristics and burden of illness (Abstract SA-PO278) The session containing this poster is scheduled for Saturday, November 9, 2019, from 10:00am-12:00pm ET.


   

Pilot study of reloxaliase in subjects with severe enteric hyperoxaluria and hyperoxalemia: A pro tem analysis of study ALLN-177-206 (Abstract FR-PO316) The session containing this poster is scheduled for Friday, November 8, 2019, from 10:00am-12:00pm ET.

Conference Call Information:

Allena Pharmaceuticals will host a live conference call and webcast at 8:30 a.m. ET today to discuss these clinical data. The conference call may be accessed by dialing (866) 521-3704 (domestic) and (210) 874-7779 (international) and referring to conference ID 3040287. A webcast of the conference call will be available in the Investors section of the Allena website at ir.allenapharma.com. The archived webcast will be available on Allena’s website approximately two hours after the conference call and will be available for 90 days following the call.

About the URIROX Program

Allena’s URIROX program consists of two pivotal Phase 3 trials, URIROX-1 and URIROX-2, which are designed to evaluate the safety and efficacy of reloxaliase in patients with enteric hyperoxaluria.

URIROX-2 is a multicenter, global, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of reloxaliase in patients with enteric hyperoxaluria, over a minimum treatment period of two years. The trial is designed to enroll 400 patients with 24-hour UOx excretion greater than or equal to 50 mg and a history of kidney stones, and will include patients with normal kidney function as well as chronic kidney disease.

The primary efficacy endpoint of URIROX-2 is the percent change from baseline in 24-hour UOx excretion during Weeks 1-4, comparing reduction in the average UOx excretion across Weeks 1-4 with reloxaliase to placebo, the same primary endpoint as URIROX-1. Secondary endpoints in URIROX-2 include the proportion of subjects with a ³ 20% reduction from baseline in 24-hour UOx excretion during Weeks 1-4 and percent change from baseline in 24-hour UOx excretion during Weeks 16 to 24. The primary long-term efficacy endpoint to confirm clinical benefit is the proportion of subjects with kidney stone disease progression, defined as a composite of either symptomatic kidney stones or finding of new or enlarged kidney stones using imaging, over a minimum treatment period of two years. Secondary long-term efficacy endpoints to confirm clinical benefit include change in eGFR from baseline and emergency room visits, hospitalizations or procedures for the management of kidney stones.

In January 2019, Allena announced that it reached alignment with the U.S. Food and Drug Administration (FDA) on both the design of URIROX-2 and its strategy to pursue a Biologics License Application (BLA) submission for reloxaliase in patients with enteric hyperoxaluria using the accelerated approval regulatory pathway.

In March 2019, Allena announced an agreement with the Duke Clinical Research Institute, a leading academic research institute within Duke University School of Medicine, to establish and lead an Academic Coordinating Center in support of the URIROX-2 Phase 3 clinical trial and preparation for the potential launch of reloxaliase.

About Study 206

Study 206 is a multi-center, open-label, single-arm Phase 2 clinical trial designed to enroll between 15 and 20 patients in the United States and Europe aged 12 and older. Patients orally administer ~240 mg (equivalent to 7,500 units) of reloxaliase with each meal or snack five times a day, for 12 consecutive weeks. The primary endpoints of the trial are change from baseline in 24-hour UOx excretion and POx levels. UOx is collected only for patients who are not on dialysis.

About Hyperoxaluria

Hyperoxaluria is a metabolic disorder characterized by significantly elevated oxalate levels in the urine, due to either overproduction of oxalate by the liver from a genetic defect, called primary hyperoxaluria, or from the excess absorption of oxalate from the diet, called secondary hyperoxaluria. Secondary hyperoxaluria is further characterized either as enteric, resulting from a chronic and unremediable underlying gastrointestinal disorder associated with malabsorption, such as bariatric surgery complications or Crohn’s disease, which predisposes patients to excess oxalate absorption, or idiopathic, meaning the underlying cause is unknown. Kidney stones, typically the first sign of hyperoxaluria, are often painful and may require interventional procedures. Severe hyperoxaluria in settings of enteric and primary hyperoxaluria may also lead to kidney damage (nephrocalcinosis), chronic kidney disease and end-stage renal disease, which may lead to death.


EH is the more severe subset of secondary hyperoxaluria. Allena estimates that there are approximately 250,000 EH patients with kidney stones and/or CKD in the United States.

About Reloxaliase

Reloxaliase is an orally-administered, recombinant oxalate-degrading enzyme that is being developed for the treatment of hyperoxaluria. Reloxaliase targets oxalate in the GI tract in an effort to reduce the burden of both dietary and endogenously produced oxalate. Reloxaliase has the potential to decrease the oxalate available systemically for deposition as calcium oxalate crystals or stones in the kidneys, as well as reduce long-term kidney complications. In addition, reloxaliase has been granted separate orphan drug designations by the FDA for the treatment of primary hyperoxaluria and for the treatment of pediatric hyperoxaluria. The European Commission has granted orphan drug designation for reloxaliase for the treatment of primary hyperoxaluria.

About Allena Pharmaceuticals

Allena Pharmaceuticals, Inc. is a late-stage biopharmaceutical company dedicated to developing and commercializing first-in-class, oral enzyme therapeutics to treat patients with rare and severe metabolic and kidney disorders. Allena’s lead product candidate, reloxaliase, is a first-in-class, oral enzyme therapeutic for the treatment of hyperoxaluria, a metabolic disorder characterized by markedly elevated urinary oxalate levels and commonly associated with kidney stones, chronic kidney disease and other serious kidney disorders.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the topline data from the URIROX-1 clinical trial and Study 206, Allena’s ongoing review of these data and implications for the future clinical, regulatory and commercial potential of reloxaliase, statements regarding the ability of reloxaliase to provide clinical benefit to patients, statements regarding future plans for the URIROX-2 clinical trial, including the adaptive design elements of this trial, statements regarding the future development of reloxaliase for patients with EH and advanced CKD, statements regarding the URIROX clinical program generally and alignment with the FDA, and statements regarding Allena’s ability to utilize the accelerated approval regulatory pathway for reloxaliase. In addition, it should be noted that additional capital will be required to complete the planned URIROX-2 clinical trial, which capital may not be available to Allena on terms that are acceptable to it, if at all. If adequate funds are not available on a timely basis, Allena may be required to delay, limit, reduce or terminate its clinical development of reloxaliase. Any forward- looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that Allena’s clinical and regulatory strategy for reloxaliase may evolve following further review of the topline data from the URIROX-1 clinical trial and Study 206, including without limitation, modifications or termination of the planned URIROX-2 clinical trial; the risk that the results of the URIROX-1 clinical trial may not be replicated in the URIROX-2 or other clinical trials of reloxaliase; the risk that the reduction in 24-hour UOx excretion observed in the placebo arm of the URIROX-1 trial may be observed in the URIROX-2 or other clinical trials of reloxaliase, which may have a negative impact on Allena’s ability to secure regulatory approval for this product candidate; the risk that results of earlier studies, or interim results, may not be predictive of future clinical trial results, and planned and ongoing studies may not establish an adequate safety or efficacy profile for reloxaliase to support regulatory approval or the use of the accelerated approval regulatory pathway; risks related to Allena’s ability to utilize the accelerated approval pathway for reloxaliase, including the risk that available data at the time of any sample size re-estimation or interim analysis conducted during the URIROX-2 trial may not be sufficient to demonstrate an increased probability of kidney stone events in patients with enteric hyperoxaluria and increasing UOx levels; the risk that the FDA may require that Allena increase the sample size or duration of treatment following the sample size reassessments to be conducted in accordance with the adaptive design element of the trial or otherwise collect additional clinical data from the


URIROX-2 or other clinical trials prior to submitting a BLA for reloxaliase; risks associated with Allena’s ability to enroll a sufficient number of patients to adequately power URIROX-2 in order to achieve ultimate statistical success for kidney stone disease progression in the long-term follow-up phase of the trial; risks related to Allena’s use of UOx and/or POx as surrogate endpoints in its ongoing clinical trials, neither of which it believes have been previously utilized as biomarkers to support regulatory approval of other drug candidates, and the risks related to validating that reductions in UOx and/or POx correlate with meaningful clinical benefit; risks associated with obtaining, maintaining and protecting intellectual property; risks associated with Allena’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; the risk of competition from other companies developing products for similar uses; risk associated with Allena’s financial condition and its need to obtain additional funding to support its business activities, including the future clinical development of reloxaliase; and risks associated with Allena’s dependence on third parties. For a discussion of other risks and uncertainties, and other important factors, any of which could cause Allena’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Item 1A of Part II of Allena’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, as well as discussions of potential risks, uncertainties and other important factors in Allena’s subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Allena undertakes no duty to update this information unless required by law.

Investor Contact

Hannah Deresiewicz

Stern Investor Relations, Inc.

212-362-1200

hannah.deresiewicz@sternir.com

Media Contact

Adam Daley

Berry & Company Public Relations

212-253-8881

adaley@berrypr.com

EX-99.2

Exhibit 99.2 URIROX-1 and Study 206 Topline Results November 7, 2019Exhibit 99.2 URIROX-1 and Study 206 Topline Results November 7, 2019


Allena Pharmaceuticals, Inc. These slides, and the accompanying presentation, contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking statements. All forward-looking statements are based on estimates and assumptions by our management that, although we believe them to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected, including those risks and uncertainties that are described under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2Allena Pharmaceuticals, Inc. These slides, and the accompanying presentation, contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking statements. All forward-looking statements are based on estimates and assumptions by our management that, although we believe them to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected, including those risks and uncertainties that are described under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2


Positive Topline Results from URIROX-1 and Study 206 Achieved Primary Endpoint: URIROX-2 Positioned for ✓ Highly statistically significant treatment Success difference (p=0.004), and a 23% reduction in 24- - Same UOx primary endpoint hour UOx from baseline on reloxaliase - URIROX-2 sized for long-term ✓ High UOx and kidney stone burden confirmatory endpoint ✓ Consistent with Phase 2 studies (overpowered for UOx) ✓ Sustained over four weeks of treatment - Adaptive design ✓ Safe and well-tolerated Opportunity to Explore Additional Registrational Path in EH Patients with Advanced CKD: ✓ 2 patients with CKD Stage 3: reduction in UOx of 29% and 42%, and POx of 42% and 16% ✓ 6 patients with CKD Stage 5: reduction in POx ranged from 27% to 68% 3Positive Topline Results from URIROX-1 and Study 206 Achieved Primary Endpoint: URIROX-2 Positioned for ✓ Highly statistically significant treatment Success difference (p=0.004), and a 23% reduction in 24- - Same UOx primary endpoint hour UOx from baseline on reloxaliase - URIROX-2 sized for long-term ✓ High UOx and kidney stone burden confirmatory endpoint ✓ Consistent with Phase 2 studies (overpowered for UOx) ✓ Sustained over four weeks of treatment - Adaptive design ✓ Safe and well-tolerated Opportunity to Explore Additional Registrational Path in EH Patients with Advanced CKD: ✓ 2 patients with CKD Stage 3: reduction in UOx of 29% and 42%, and POx of 42% and 16% ✓ 6 patients with CKD Stage 5: reduction in POx ranged from 27% to 68% 3


Pioneering Technology in Formulation Oral Enzyme Therapeutics Proprietary Technology development approach Therapeutic Platform Oral Enzyme GI MOA Therapeutic candidates Leverage GI that degrade a specific tract as metabolite “auxiliary kidney” Reloxaliase ALLN-346 Non-absorbed Reduces potential for adverse events 4Pioneering Technology in Formulation Oral Enzyme Therapeutics Proprietary Technology development approach Therapeutic Platform Oral Enzyme GI MOA Therapeutic candidates Leverage GI that degrade a specific tract as metabolite “auxiliary kidney” Reloxaliase ALLN-346 Non-absorbed Reduces potential for adverse events 4


Enteric Hyperoxaluria – Disease Overview Gastrointestinal Tract Enteric Hyperoxaluria (EH) Dietary Oxalate Enteric: Pertaining to the intestinal tract Hyper: High or excess Oxal: Oxalate Uria: In the urine Definition: Excess absorption of oxalate in the GI tract due to gastric bypass surgery, inflammatory bowel disease, short bowel syndrome, celiac disease and Oxalate chronic pancreatitis Consequence: Kidney stones and calcium oxalate crystal deposits in the kidneys which can lead to inflammation, CKD and ESRD There are no FDA-approved pharmacological therapies to treat any form of hyperoxaluria Inflammation, Kidney Stones CKD and ESRD 5Enteric Hyperoxaluria – Disease Overview Gastrointestinal Tract Enteric Hyperoxaluria (EH) Dietary Oxalate Enteric: Pertaining to the intestinal tract Hyper: High or excess Oxal: Oxalate Uria: In the urine Definition: Excess absorption of oxalate in the GI tract due to gastric bypass surgery, inflammatory bowel disease, short bowel syndrome, celiac disease and Oxalate chronic pancreatitis Consequence: Kidney stones and calcium oxalate crystal deposits in the kidneys which can lead to inflammation, CKD and ESRD There are no FDA-approved pharmacological therapies to treat any form of hyperoxaluria Inflammation, Kidney Stones CKD and ESRD 5


Reloxaliase: First-in-class Therapeutic Candidate for EH Mechanism of Action Target Product Characteristics Oxalate Degradation in the Gastrointestinal Tract Crystalline Oxalate-Specific Enzyme Oxalate Oral Capsule Formulation Taken with Food Non-Absorbed/Non-Systemic Reloxaliase Room Temperature Stability By-Products for Excretion 6Reloxaliase: First-in-class Therapeutic Candidate for EH Mechanism of Action Target Product Characteristics Oxalate Degradation in the Gastrointestinal Tract Crystalline Oxalate-Specific Enzyme Oxalate Oral Capsule Formulation Taken with Food Non-Absorbed/Non-Systemic Reloxaliase Room Temperature Stability By-Products for Excretion 6


Reloxaliase Development Program Addresses the Full Spectrum of Disease Study Population: Enteric Hyperoxaluria with Enteric Hyperoxaluria CKD and Hyperoxalemia Normal/CKD 1 CKD 2 CKD 3 CKD 4 ESRD • The clinical literature suggests that a ≥ 20% reduction in urine oxalate (UOx) could result in a 25-50% lower incidence of kidney stone recurrence, and may increase renal 1 survival • By reducing oxalate levels, potential to slow CKD progression, enable kidney transplant and protect new kidney post- transplant 1 1Borghi N et al. Eng J Med. 2002; Taylor and Curhan, Kidney Int. 2008; Curhan GC et al., J Am Soc Nephrol., 2017; Zhao et al. Clin J Am Soc Nephrol. 2016 Normal Dialysis 7 Oxalate BurdenReloxaliase Development Program Addresses the Full Spectrum of Disease Study Population: Enteric Hyperoxaluria with Enteric Hyperoxaluria CKD and Hyperoxalemia Normal/CKD 1 CKD 2 CKD 3 CKD 4 ESRD • The clinical literature suggests that a ≥ 20% reduction in urine oxalate (UOx) could result in a 25-50% lower incidence of kidney stone recurrence, and may increase renal 1 survival • By reducing oxalate levels, potential to slow CKD progression, enable kidney transplant and protect new kidney post- transplant 1 1Borghi N et al. Eng J Med. 2002; Taylor and Curhan, Kidney Int. 2008; Curhan GC et al., J Am Soc Nephrol., 2017; Zhao et al. Clin J Am Soc Nephrol. 2016 Normal Dialysis 7 Oxalate Burden


URIROX-1: Evaluate the Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria UOx ≥ 50mg/24h Normal to Stage 3 CKD Reloxaliase Follow up (eGFR ≥ 30) 4 weeks Reloxaliase (7,500 u) or placebo 2 cap with Screening Randomization meal/snack 3 to 5 times per day x 28 days 1:1 N=115 Placebo 1x UOx 2x UOx 2x UOx 2x UOx 2x UOx 2x UOx Primary Endpoint: • Percent change from baseline in 24h UOx excretion during Weeks 1 to 4 Key Secondary Endpoint: • Proportion of subjects with a ≥ 20% reduction from baseline in 24h UOx excretion during Weeks 1 to 4 Pre-specified, Stratified Analysis • Subset analysis of the primary and lead secondary endpoint in subjects with a history of bariatric surgery 8URIROX-1: Evaluate the Safety and Efficacy of Reloxaliase in Patients with Enteric Hyperoxaluria UOx ≥ 50mg/24h Normal to Stage 3 CKD Reloxaliase Follow up (eGFR ≥ 30) 4 weeks Reloxaliase (7,500 u) or placebo 2 cap with Screening Randomization meal/snack 3 to 5 times per day x 28 days 1:1 N=115 Placebo 1x UOx 2x UOx 2x UOx 2x UOx 2x UOx 2x UOx Primary Endpoint: • Percent change from baseline in 24h UOx excretion during Weeks 1 to 4 Key Secondary Endpoint: • Proportion of subjects with a ≥ 20% reduction from baseline in 24h UOx excretion during Weeks 1 to 4 Pre-specified, Stratified Analysis • Subset analysis of the primary and lead secondary endpoint in subjects with a history of bariatric surgery 8


URIROX-1: Patient Demographics and Baseline Characteristics Reloxaliase Placebo High Burden of Disease Category / Statistic (N=58) (N=57) Age (years) – Mean (SD) 58.7 (10.09) 58.6 (10.18) Baseline UOx of 89.2 mg/day Gender, n (%) Female 28 (48.3) 27 (47.4) Enteric condition, n (%) Average 11 stone events in Bariatric surgery [Roux-en-Y gastric bypass] 40 (69.0) [27 (46.6)] 38 (66.7) [27 (47.4)] Inflammatory bowel disease 10 (17.2) 10 (17.5) last 5 years Short bowel syndrome 3 (5.2) 8 (14.0) Pancreatic insufficiency 3 5.2) 0 Other 2 (3.4) 1 (1.8) 16.5% reported KS events Baseline UOx (mg/24h) – Mean (SD) 87.3 (28.87) 91.1 (41.64) 1 during study Baseline UOx ≥ 90 mg/24h, n (%) 22 (37.9) 23 (40.4) Number of kidney stone episodes in past 5 years- Mean (SD) 8.8 (27.49) 14.2 (43.23) 26% CKD Stage 3 2 eGFR (mL/min/1.73m ) - Mean (SD) 76.4 (22.71) 80.5 (24.60) CKD Stage 3, n (%) 16 (27.6) 14 (24.6) 1. Kidney stone events during the study period were approximately equally distributed between treatment and placebo groups 9URIROX-1: Patient Demographics and Baseline Characteristics Reloxaliase Placebo High Burden of Disease Category / Statistic (N=58) (N=57) Age (years) – Mean (SD) 58.7 (10.09) 58.6 (10.18) Baseline UOx of 89.2 mg/day Gender, n (%) Female 28 (48.3) 27 (47.4) Enteric condition, n (%) Average 11 stone events in Bariatric surgery [Roux-en-Y gastric bypass] 40 (69.0) [27 (46.6)] 38 (66.7) [27 (47.4)] Inflammatory bowel disease 10 (17.2) 10 (17.5) last 5 years Short bowel syndrome 3 (5.2) 8 (14.0) Pancreatic insufficiency 3 5.2) 0 Other 2 (3.4) 1 (1.8) 16.5% reported KS events Baseline UOx (mg/24h) – Mean (SD) 87.3 (28.87) 91.1 (41.64) 1 during study Baseline UOx ≥ 90 mg/24h, n (%) 22 (37.9) 23 (40.4) Number of kidney stone episodes in past 5 years- Mean (SD) 8.8 (27.49) 14.2 (43.23) 26% CKD Stage 3 2 eGFR (mL/min/1.73m ) - Mean (SD) 76.4 (22.71) 80.5 (24.60) CKD Stage 3, n (%) 16 (27.6) 14 (24.6) 1. Kidney stone events during the study period were approximately equally distributed between treatment and placebo groups 9


URIROX-1 Primary Endpoint: Statistically Significant Reduction of UOx URIROX-1 N=115 Reloxaliase Placebo n=58 n=57 0 Achieved primary endpoint Highly statistically significant -5 response verses placebo -10 (P=0.004) -9.7 -15 22.6% reduction in UOx from baseline (LS mean) -20 -14.3% LS mean treatment -22.6 -25 difference p=0.004* -30 *Percent change from Baseline in 24-hour UOx excretion during Weeks 1 to 4 10 Percent Change in UOx (%)URIROX-1 Primary Endpoint: Statistically Significant Reduction of UOx URIROX-1 N=115 Reloxaliase Placebo n=58 n=57 0 Achieved primary endpoint Highly statistically significant -5 response verses placebo -10 (P=0.004) -9.7 -15 22.6% reduction in UOx from baseline (LS mean) -20 -14.3% LS mean treatment -22.6 -25 difference p=0.004* -30 *Percent change from Baseline in 24-hour UOx excretion during Weeks 1 to 4 10 Percent Change in UOx (%)


URIROX-1: Summary of Efficacy Pre-Specified Sub-Population Overall Population Analysis Bariatric Bariatric Reloxaliase Placebo Reloxaliase Placebo (N=58) (N=57) (N=40) (N=38) PRIMARY ENDPOINT: Percent change in 24h UOx from Baseline during Weeks 1-4 a Comparison in percent change from baseline b LS mean relative ratio (95% CI) -14.329 (-22.81, -4.92) -16.190 (-26.68, -4.20) P-value 0.004 0.010 SECONDARY ENDPOINT: Proportion with ≥20% Reduction in 24h UOx from Baseline during Weeks 1-4 n/N (%) 28/58 (48.3) 18/57 (31.6) 20/40 (50.0) 11/38 (28.9) c Comparison between treatments 2.141 (0.97, 4.74) 2.891 (1.07, 7.82) Odds ratio (95% CI) P-value 0.061 0.036 CI, confidence interval; LS, least squares; MMRM, mixed model repeated measures; N, number of subjects dosed; SE, standard error a Baseline is defined as the average of the UOx values derived from the two baseline 24-hour urine collections prior to randomization. b LS means, CIs, and p-values are based on an MMRM model. c Odd ratio, confidence interval, and p-value are from a stratified logistic regression model. 11URIROX-1: Summary of Efficacy Pre-Specified Sub-Population Overall Population Analysis Bariatric Bariatric Reloxaliase Placebo Reloxaliase Placebo (N=58) (N=57) (N=40) (N=38) PRIMARY ENDPOINT: Percent change in 24h UOx from Baseline during Weeks 1-4 a Comparison in percent change from baseline b LS mean relative ratio (95% CI) -14.329 (-22.81, -4.92) -16.190 (-26.68, -4.20) P-value 0.004 0.010 SECONDARY ENDPOINT: Proportion with ≥20% Reduction in 24h UOx from Baseline during Weeks 1-4 n/N (%) 28/58 (48.3) 18/57 (31.6) 20/40 (50.0) 11/38 (28.9) c Comparison between treatments 2.141 (0.97, 4.74) 2.891 (1.07, 7.82) Odds ratio (95% CI) P-value 0.061 0.036 CI, confidence interval; LS, least squares; MMRM, mixed model repeated measures; N, number of subjects dosed; SE, standard error a Baseline is defined as the average of the UOx values derived from the two baseline 24-hour urine collections prior to randomization. b LS means, CIs, and p-values are based on an MMRM model. c Odd ratio, confidence interval, and p-value are from a stratified logistic regression model. 11


Consistent Reloxaliase Treatment Effect Across Phase 2 and Phase 3 Studies Consistent reduction in UOx of ≥ 20% from baseline in reloxaliase treated patients Highly significant response in pivotal trial compared to placebo (P=0.004) Well tolerated Study 396 (4 Days) Study 713 (4 Weeks) Study 206 (12 Weeks ) URIROX-1 (4 Weeks ) Phase 3 Phase 3 Phase 3 Overall Criteria Criteria Criteria EH Overall EH ≥ 50 mg/24h ≥ 50 mg/24h Reloxaliase CKD 3b EH (n=2) (n=11) (n=5) EH (n=3) EH (n=10) n=58 0 0 0 0 -5 -5 -5 -5 -10% -10 -10 -10 -10 -15 -15 -15 -15 -20% -24% -24% -23% -20 -20 -20 -20 -25 -25 -25 -25 -35% -30 -30 -30 -30 -35 -35 -35 -35 -40 -40 -40 -40 ◼ UOx Presented at ASN 2014 Presented at ASN 2017 Presented at OHF 2019 Presented at ASN 2019 Study 206 UOx adjusted to creatinine (Cr) to correct for renal dysfunction. Data shown with Phase 3 entry criteria is based on a post hoc analysis 12 Percent Change in UOx (%) LS Mean Percent Change in UOx (%) Percent Change in UOx (%) LS Mean Percent Change in UOx (%)Consistent Reloxaliase Treatment Effect Across Phase 2 and Phase 3 Studies Consistent reduction in UOx of ≥ 20% from baseline in reloxaliase treated patients Highly significant response in pivotal trial compared to placebo (P=0.004) Well tolerated Study 396 (4 Days) Study 713 (4 Weeks) Study 206 (12 Weeks ) URIROX-1 (4 Weeks ) Phase 3 Phase 3 Phase 3 Overall Criteria Criteria Criteria EH Overall EH ≥ 50 mg/24h ≥ 50 mg/24h Reloxaliase CKD 3b EH (n=2) (n=11) (n=5) EH (n=3) EH (n=10) n=58 0 0 0 0 -5 -5 -5 -5 -10% -10 -10 -10 -10 -15 -15 -15 -15 -20% -24% -24% -23% -20 -20 -20 -20 -25 -25 -25 -25 -35% -30 -30 -30 -30 -35 -35 -35 -35 -40 -40 -40 -40 ◼ UOx Presented at ASN 2014 Presented at ASN 2017 Presented at OHF 2019 Presented at ASN 2019 Study 206 UOx adjusted to creatinine (Cr) to correct for renal dysfunction. Data shown with Phase 3 entry criteria is based on a post hoc analysis 12 Percent Change in UOx (%) LS Mean Percent Change in UOx (%) Percent Change in UOx (%) LS Mean Percent Change in UOx (%)


Reloxaliase Demonstrates Sustained Reductions in UOx Across Weeks 1-4 URIROX-1 0 Week 1 Week 2 Week 3 Week 4 -5 -10 -15 -20 -25 Reloxaliase Placebo -30 13 Percent Change in UOx (%)Reloxaliase Demonstrates Sustained Reductions in UOx Across Weeks 1-4 URIROX-1 0 Week 1 Week 2 Week 3 Week 4 -5 -10 -15 -20 -25 Reloxaliase Placebo -30 13 Percent Change in UOx (%)


Reloxaliase Generally Well-Tolerated in Clinical Trials to Date Study 396 Study 649 Study 713 URIROX-1 All Reloxaliase Placebo Reloxaliase Placebo Reloxaliase Placebo (n=16) (n=30) (n=24) (n=32) (n=35) (n=58) (n=57) n (%) n (%) n (%) n (%) n (%) n (%) n (%) 1 TEAE 9 (56.3%) 13 (43.3%) 6 (25.0%) 16 (50%) 22 (62.9%) 40 (69.0%) 30 (52.6%) 4 Severe TEAE 0 0 0 0 0 1 (1.7) 0 Related TEAE 2 (12.5%) 5 (16.7%) 2 (8.3%) 3 (9.4%) 8 (22.9%) 17 (29.3%) 11 (19.3%) 2 4 Serious AE (SAE) 0 1 (3.3%) 0 0 0 1 (1.7%) 0 Related SAEs 0 0 0 0 0 0 0 AEs Leading to Study Drug 2 3 0 1 (3.3%) 0 0 2 (5.7%) 0 1 (1.8%) Withdrawal AEs Leading to Death 0 0 0 0 0 0 0 1. TEAE = Treatment emergent adverse events are defined as AEs with onset at the time of or following the first dose of treatment with study drug through 7 days after their last dose of study medication, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment through 7 days after their last dose of study medication. 2. One subject reported congestive heart failure of moderate severity, considered not related to study drug, but secondary to a recent cardioversion for atrial fibrillation. This resulted in hospitalization and withdrawal from the study; same subject in both rows. 3. Two placebo treated subjects withdrew from study drug, one after nearly 4 weeks of treatment due to nausea, considered not related, and another due to hives/dermatitis with onset 3 days after starting placebo, considered possibly related. 4. Unrelated to reloxaliase 14Reloxaliase Generally Well-Tolerated in Clinical Trials to Date Study 396 Study 649 Study 713 URIROX-1 All Reloxaliase Placebo Reloxaliase Placebo Reloxaliase Placebo (n=16) (n=30) (n=24) (n=32) (n=35) (n=58) (n=57) n (%) n (%) n (%) n (%) n (%) n (%) n (%) 1 TEAE 9 (56.3%) 13 (43.3%) 6 (25.0%) 16 (50%) 22 (62.9%) 40 (69.0%) 30 (52.6%) 4 Severe TEAE 0 0 0 0 0 1 (1.7) 0 Related TEAE 2 (12.5%) 5 (16.7%) 2 (8.3%) 3 (9.4%) 8 (22.9%) 17 (29.3%) 11 (19.3%) 2 4 Serious AE (SAE) 0 1 (3.3%) 0 0 0 1 (1.7%) 0 Related SAEs 0 0 0 0 0 0 0 AEs Leading to Study Drug 2 3 0 1 (3.3%) 0 0 2 (5.7%) 0 1 (1.8%) Withdrawal AEs Leading to Death 0 0 0 0 0 0 0 1. TEAE = Treatment emergent adverse events are defined as AEs with onset at the time of or following the first dose of treatment with study drug through 7 days after their last dose of study medication, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment through 7 days after their last dose of study medication. 2. One subject reported congestive heart failure of moderate severity, considered not related to study drug, but secondary to a recent cardioversion for atrial fibrillation. This resulted in hospitalization and withdrawal from the study; same subject in both rows. 3. Two placebo treated subjects withdrew from study drug, one after nearly 4 weeks of treatment due to nausea, considered not related, and another due to hives/dermatitis with onset 3 days after starting placebo, considered possibly related. 4. Unrelated to reloxaliase 14


Phase 3 Program Design for Accelerated Approval Strategy Week 4: Reloxaliase Follow up 4 weeks N=115 (1:1) Placebo UOx ≥ 50mg/24h, Normal to Stage 3 CKD (eGFR ≥ 30) Week 24: RCT follow-up for Reloxaliase (7,500 u) or placebo 2 BLA submission cap with meal/snack 3-5 x per day minimum of 2 years data set Reloxaliase Follow up 4 weeks N≈400 (1:1) Placebo POST-APPROVAL CONFIRMATORY ENDPOINTS PRIMARY ENDPOINT SECONDARY ENDPOINT Primary: Kidney stone disease progression Percent change from baseline in 24h Percent change from Secondary: Change in eGFR and ER visits / UOx excretion during Weeks 1 to 4 baseline in 24h UOx excretion hospitalizations / procedures for management during Weeks 16 to 24 SECONDARY ENDPOINT of kidney stones Proportion of subjects with a ≥ 20% ADDITIONAL FILING DATA ELEMENTS reduction from baseline in 24h UOx • Model of relationship between during Weeks 1-4 UOx and KS events, informed by data from the study • Sufficient conditional power to meet long term primary endpoint 15Phase 3 Program Design for Accelerated Approval Strategy Week 4: Reloxaliase Follow up 4 weeks N=115 (1:1) Placebo UOx ≥ 50mg/24h, Normal to Stage 3 CKD (eGFR ≥ 30) Week 24: RCT follow-up for Reloxaliase (7,500 u) or placebo 2 BLA submission cap with meal/snack 3-5 x per day minimum of 2 years data set Reloxaliase Follow up 4 weeks N≈400 (1:1) Placebo POST-APPROVAL CONFIRMATORY ENDPOINTS PRIMARY ENDPOINT SECONDARY ENDPOINT Primary: Kidney stone disease progression Percent change from baseline in 24h Percent change from Secondary: Change in eGFR and ER visits / UOx excretion during Weeks 1 to 4 baseline in 24h UOx excretion hospitalizations / procedures for management during Weeks 16 to 24 SECONDARY ENDPOINT of kidney stones Proportion of subjects with a ≥ 20% ADDITIONAL FILING DATA ELEMENTS reduction from baseline in 24h UOx • Model of relationship between during Weeks 1-4 UOx and KS events, informed by data from the study • Sufficient conditional power to meet long term primary endpoint 15


Positive URIROX-1 Results Highlight Potential for Accelerated Approval Submission and Provide Insights for URIROX-2 Success Accelerated Approval Submission Post-Approval Confirmatory Endpoints • URIROX-2 shares common UOx primary • UOx decrease in placebo group not expected to be endpoint and key secondary endpoints sustained in longer URIROX-2 study due to less frequent with URIROX-1 urine collections and difficulty maintaining dietary changes for 2+ years • Sized for demonstrating long-term clinical benefit, URIROX-2 is overpowered to • Literature review of metabolic disease studies suggests achieve UOx primary endpoint (n~400) that treatment response is retained or improved over 1 time despite placebo effect (e.g., phosphate, glucose) • Consistent and sustained reloxaliase treatment effect• URIROX-2 kidney stone event rate modeled conservatively based on medical records and claims • Continued attractive tolerability profile • URIROX-2 will also capture asymptomatic events via imaging • URIROX-1 data suggests high rate of stone events • Adaptive design with two sample size reassessments (N=240, N=400) to ensure adequacy of the trial to achieve long-term endpoint 1. Block GA et al. AJKD. 2015;65(5):728-736; Khan A et al. Diabetes Care 2018;41:994–100 16Positive URIROX-1 Results Highlight Potential for Accelerated Approval Submission and Provide Insights for URIROX-2 Success Accelerated Approval Submission Post-Approval Confirmatory Endpoints • URIROX-2 shares common UOx primary • UOx decrease in placebo group not expected to be endpoint and key secondary endpoints sustained in longer URIROX-2 study due to less frequent with URIROX-1 urine collections and difficulty maintaining dietary changes for 2+ years • Sized for demonstrating long-term clinical benefit, URIROX-2 is overpowered to • Literature review of metabolic disease studies suggests achieve UOx primary endpoint (n~400) that treatment response is retained or improved over 1 time despite placebo effect (e.g., phosphate, glucose) • Consistent and sustained reloxaliase treatment effect• URIROX-2 kidney stone event rate modeled conservatively based on medical records and claims • Continued attractive tolerability profile • URIROX-2 will also capture asymptomatic events via imaging • URIROX-1 data suggests high rate of stone events • Adaptive design with two sample size reassessments (N=240, N=400) to ensure adequacy of the trial to achieve long-term endpoint 1. Block GA et al. AJKD. 2015;65(5):728-736; Khan A et al. Diabetes Care 2018;41:994–100 16


Reloxaliase has Potential to Benefit EH Patients With Advanced CKD EH Patients with CKD can Progress to ESRD Patient Presents Progression to Dialysis Kidney Transplant with CKD Stage 5 CKD Procedure t URIROX-2 Study 206 Opportunity * Population Population Delay CKD Progression 1 Delay progression to more severe stages of CKD ✔✔ Increase Lower oxalate levels in EH patients seeking a transplant, Pre-Transplant 2 ✔ Eligibility allowing them to qualify for a transplant Improve Lower oxalate levels in the post-transplant population to Post-Transplant ✔ decrease the chance of graft failure and/or renal 3 Graft Success function decline t URIROX-2 Long-Term efficacy endpoints include change in estimated glomerular filtration rate (eGFR) from Baseline *Potential clinical outcomes to be assessed in future studies 17Reloxaliase has Potential to Benefit EH Patients With Advanced CKD EH Patients with CKD can Progress to ESRD Patient Presents Progression to Dialysis Kidney Transplant with CKD Stage 5 CKD Procedure t URIROX-2 Study 206 Opportunity * Population Population Delay CKD Progression 1 Delay progression to more severe stages of CKD ✔✔ Increase Lower oxalate levels in EH patients seeking a transplant, Pre-Transplant 2 ✔ Eligibility allowing them to qualify for a transplant Improve Lower oxalate levels in the post-transplant population to Post-Transplant ✔ decrease the chance of graft failure and/or renal 3 Graft Success function decline t URIROX-2 Long-Term efficacy endpoints include change in estimated glomerular filtration rate (eGFR) from Baseline *Potential clinical outcomes to be assessed in future studies 17


Study 206: Reloxaliase Demonstrates Robust Reduction in Oxalate Burden in Eight EH Patients with Advanced CKD Fat Pancreatic Crohn’s Crohn’s Short Bowel RYGB RYGB*/** Crohn’s Disease Malabsorption Insufficiency* Disease** Disease Syndrome CKD Stage 5 CKD Stage 5 CKD Stage 5 CKD 3T CKD Stage 5T CKD Stage 5 CKD Stage 5T CKD 3b Baseline POx Baseline POx Baseline POx UOx/Cr 210 Baseline POx Baseline POx Baseline POx UOx/Cr 98 47 µmol/L 68 µmol/L 40 µmol/L POx 9 µmol/L 104 µmol/L 19 µmol/L 52 µmol/L POx 7 µmol/L 0 -10 -16% -19% -20 ∆ = 1 ∆ = 13 -27% -29% -29% µmol/L µmol/L -30 ∆ = 14 ∆ = 29 ∆ = 14 µmol/L mg/g µmol/L -42% -42% -40 -45% -49% ∆ = 88 ∆ = 3 ∆ = 47 mg/g µmol/L -50 µmol/L ∆ = 20 µmol/L -60 -68% -70 ∆ = 13 UOx POx µmol/L -80 Urinary Oxalate (UOx mg/d) was normalized to creatinine mg/g; UOx reduction was calculated as a mean change from baseline using 2 UOx measurements over 12 weeks; UOx was not measured in subjects on dialysis or on subjects with eGFR ≤ 15 ml/min/1.73m Plasma oxalate (POx µmol/L) reduction was calculated as a mean change from baseline using POx measurements over 12 weeks. *Subject had only 1 POx sample during the study 18 **Subject treatment ongoing 18 Percent Change in UOx and POx (%)Study 206: Reloxaliase Demonstrates Robust Reduction in Oxalate Burden in Eight EH Patients with Advanced CKD Fat Pancreatic Crohn’s Crohn’s Short Bowel RYGB RYGB*/** Crohn’s Disease Malabsorption Insufficiency* Disease** Disease Syndrome CKD Stage 5 CKD Stage 5 CKD Stage 5 CKD 3T CKD Stage 5T CKD Stage 5 CKD Stage 5T CKD 3b Baseline POx Baseline POx Baseline POx UOx/Cr 210 Baseline POx Baseline POx Baseline POx UOx/Cr 98 47 µmol/L 68 µmol/L 40 µmol/L POx 9 µmol/L 104 µmol/L 19 µmol/L 52 µmol/L POx 7 µmol/L 0 -10 -16% -19% -20 ∆ = 1 ∆ = 13 -27% -29% -29% µmol/L µmol/L -30 ∆ = 14 ∆ = 29 ∆ = 14 µmol/L mg/g µmol/L -42% -42% -40 -45% -49% ∆ = 88 ∆ = 3 ∆ = 47 mg/g µmol/L -50 µmol/L ∆ = 20 µmol/L -60 -68% -70 ∆ = 13 UOx POx µmol/L -80 Urinary Oxalate (UOx mg/d) was normalized to creatinine mg/g; UOx reduction was calculated as a mean change from baseline using 2 UOx measurements over 12 weeks; UOx was not measured in subjects on dialysis or on subjects with eGFR ≤ 15 ml/min/1.73m Plasma oxalate (POx µmol/L) reduction was calculated as a mean change from baseline using POx measurements over 12 weeks. *Subject had only 1 POx sample during the study 18 **Subject treatment ongoing 18 Percent Change in UOx and POx (%)


Reloxaliase: Therapeutic Candidate with Blockbuster Potential High Unmet Need in Enteric Hyperoxaluria (EH) Novel Non-absorbed Oral Biologic URIROX-1 Trial Achieves Primary Endpoint with Highly Significant Reduction in UOx (p=0.004) Consistent Results across Phase 2 and 3 Studies Favorable Risk Benefit Profile FDA Alignment on Accelerated Approval Strategy Potential First FDA-Approved Treatment in EH Study 206 Data Supporting Further Development in EH with Advanced CKD Worldwide Marketing Rights 19Reloxaliase: Therapeutic Candidate with Blockbuster Potential High Unmet Need in Enteric Hyperoxaluria (EH) Novel Non-absorbed Oral Biologic URIROX-1 Trial Achieves Primary Endpoint with Highly Significant Reduction in UOx (p=0.004) Consistent Results across Phase 2 and 3 Studies Favorable Risk Benefit Profile FDA Alignment on Accelerated Approval Strategy Potential First FDA-Approved Treatment in EH Study 206 Data Supporting Further Development in EH with Advanced CKD Worldwide Marketing Rights 19


ALLN-346: Platform Extension Addressing Significant Opportunity in Gout Patients with Moderate-to-Severe CKD Gout Market is Incompletely Served by Existing Therapies ~375,000 gout patients with moderate to severe CKD who have uncontrolled gout on urate lowering therapy (ULT)* Gout patients with renal impairment are not optimally managed due to limitations of existing therapies ALLN-346 Therapeutic Strategy: • Gout patients with kidney and liver problems are contraindicated for allopurinol, Uloric, and • Novel urate degrading enzyme optimized for stability in the Zurampic GI tract • Current ULT’s may interact with other • MOA: orally administered, gut restricted enzyme therapeutic medications • Co-morbidities (e.g. cardiovascular) may also • Animal POC: demonstrated a robust reduction in urine and limit ULT options plasma uric acid levels in a severe animal model of hyperuricemia with advanced CKD Significant unmet need for safe and effective therapy that can be used in patients with renal impairment • Data presented at American College of Rheumatology meeting October 22, 2018 Sources: . *Lim JJ, Fu AC, and Reasner D. Prevalence of CKD and Uncontrolled Gout Among US Adults: Results from NHANES 2007- 2012. Poster presented at: The National Kidney Foundation Spring Clinical Meetings; April 18-22, 2017; Orlando Florida. Fletcher Spaght Analysis July 2016; Image: Retailleau, P., Colloc'h, N., Vivares, D., Bonnete, F., Castro, B., El Hajji, M., Prange, T. (2005) Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation to the content of the active site. Acta Crystallogr.,Sect.D, 61, 218-229; D. Grujic Urol Res 2008, 193. 20ALLN-346: Platform Extension Addressing Significant Opportunity in Gout Patients with Moderate-to-Severe CKD Gout Market is Incompletely Served by Existing Therapies ~375,000 gout patients with moderate to severe CKD who have uncontrolled gout on urate lowering therapy (ULT)* Gout patients with renal impairment are not optimally managed due to limitations of existing therapies ALLN-346 Therapeutic Strategy: • Gout patients with kidney and liver problems are contraindicated for allopurinol, Uloric, and • Novel urate degrading enzyme optimized for stability in the Zurampic GI tract • Current ULT’s may interact with other • MOA: orally administered, gut restricted enzyme therapeutic medications • Co-morbidities (e.g. cardiovascular) may also • Animal POC: demonstrated a robust reduction in urine and limit ULT options plasma uric acid levels in a severe animal model of hyperuricemia with advanced CKD Significant unmet need for safe and effective therapy that can be used in patients with renal impairment • Data presented at American College of Rheumatology meeting October 22, 2018 Sources: . *Lim JJ, Fu AC, and Reasner D. Prevalence of CKD and Uncontrolled Gout Among US Adults: Results from NHANES 2007- 2012. Poster presented at: The National Kidney Foundation Spring Clinical Meetings; April 18-22, 2017; Orlando Florida. Fletcher Spaght Analysis July 2016; Image: Retailleau, P., Colloc'h, N., Vivares, D., Bonnete, F., Castro, B., El Hajji, M., Prange, T. (2005) Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation to the content of the active site. Acta Crystallogr.,Sect.D, 61, 218-229; D. Grujic Urol Res 2008, 193. 20


Upcoming Milestones TARGET MILESTONE STATUS 2Q19 Study 206 Initial Data ✓ 4Q19 URIROX-1 Topline Data ✓ 4Q19 Study 206 Topline Data ✓ 4Q19 ALLN-346 IND Filing On Track 2H20 ALLN-346 Initial Data On Track 2H21 URIROX-2 Topline Data On Track 21Upcoming Milestones TARGET MILESTONE STATUS 2Q19 Study 206 Initial Data ✓ 4Q19 URIROX-1 Topline Data ✓ 4Q19 Study 206 Topline Data ✓ 4Q19 ALLN-346 IND Filing On Track 2H20 ALLN-346 Initial Data On Track 2H21 URIROX-2 Topline Data On Track 21


URIROX-1 and Study 206 Topline Results November 7, 2019URIROX-1 and Study 206 Topline Results November 7, 2019